HIFU for localized prostate cancer: a series of 172 UK patients

The following commentary reports with greater accuracy and in more detail on the same article, dealing with the same series of 172 HIFU patients, as was previously discussed on this web site on July 2 this year. The original report was based solely on the abstract of the article. The current report has been posted after a careful analysis of the entire articleThere are considerable differences between the information available in the full article and the summary information provided in the abstract (which is not unusual).

So let us be extremely clear up front.

In the full report on these patients, Emberton and his colleagues have made considerable efforts to detail information that is often not provided in this type of early series of patients managed with a relatively new treatment option. And they deserve every congratulation for these efforts. In the comments that follow, your commentator is going to make every attempt to point out both the upsides and the downsides of the information that is available in the full paper.

The article addresses the treatment of 172 patients treated using the Sonoblate 500 HIFU device over a 26.5-month period at one or other of two London hospitals between February 2005 and May 2007. The patients were stratified using the D’Amico risk criteria, and included:

  • 38 low-risk patients (who had to meet all three of the following criteria: PSA ≤ 10 ng/ml; Gleason score of ≤ 6; clinical stage ≤ T2a)
  • 51 intermediate-risk patients (who had to have any one or any combination of the following: a PSA of 10.1-20.0 ng/ml;  a Gleason score of ≤ 7; clinical stage T2b)
  • 47 high-risk patients (who had to have any one or a combination of the following: a PSA > 20.0 ng/ml; a Gleason score of 8-10; clinical stage ≥ T2c)
  • 36 patients whose risk could not be assessed because relevant information was missing.

In addition, the series included 49 patients whose prostate volume was estimated to be > 40 ml (or who had a posterior to anterior prostate height of 40 mm) and who had therefore received 3 months of hormone ablation with bicalutamide 50 mg/day and a 5α-reductase inhibitor (finasteride or dutasteride) prior to HIFU therapy.

Other pretreatment data included the following:

  • All patients were clinically staged as ≤ T3bN0M0 disease.
  • No patients received a prior transurethral resection of the prostate (a TURP).
  • The mean age of the patients was 64.1 ± 8.3 years.
  • All patients were required to have an estimated prostate volume of ≤ 40 ml at the time of HIFU (whether they had received hormone ablation or not).
  • Just 49/172 patients (at one of the two centers) completed a pretreatment erectile function questionnaire.
  • Based on the results of this questionnaire we know that:
    • 24/49 were potent preoperatively if one accepts “Erections hard enough to achieve penetration a few times (much less than half the time)” or better as an acceptable level of potency
    • Only 12/49 were potent if one requires the higher criterion of “Erections hard enough to achieve penetration sometimes (about half the time)” or better as an acceptable level of potency

Since most men would only consider themselves “potent” if they  were able to achieve penetration almost always or always, we would consider the above criteria for potency to be a pretty low bar to begin with. This has implications for interpretation of the results of the study too, as we shall see later.

So what were the outcomes of the study? Ahmed et al. provide the following detailed data, not all of which is immediately apparent in the abstract of the article:

  • 172 men were treated under general anesthesia as day-case procedures.
  • 134/172 patients (78 percent) were discharged at an average of 5 h after treatment.
  • 38/172 patients (22 percent) remained in hospital for one night for monitoring for a variety of reasons.
  • Mean patient follow-up was 364 days (range: 135-759 days).
  • 52/172 patients (30.2 percent) required subsequent intervention for urethral stricture or post-HIFU clearance of necrotic tissue.
  • The incidence of post-surgical urethral stricture or necrotic tissue was significantly lower in patients given a suprapubic catheter compared with those given a urethral catheter (19.4 vs 40.4 percent).
  • Antibiotics were given to 23.8 percent of patients for presumed urinary tract infection during the 12-month follow-up period, and the rate of epididymitis was 7.6 percent.
  • Mild (Grade 1) stress urinary incontinence (requiring no pads) was reported by 12/172 patients (7.0 percent).
  • 1/172 patients (0.6 percent) reported Grade 3 urinary incontinence requiring an artificial urinary sphincter.
  • The International Prostate Symptom Score or IPSS “significantly deteriorated at 3 and 6 months” after treatment but “returned to baseline at 6 and 12 months.” In other words, there were a series of post-treatment urinary tract symptoms immediately post-treatment that affected quality of life, but these resolved within a year.
  • Neither rectal toxicity nor recto-urethral fistulae were observed.
  • 65/83 patients (78.3 percent) for whom data were available achieved a PSA nadir of  ≤ 0.5 ng/ml at 12 months
  • 48/83 patients (57.8 percent) achieved a PSA nadir of  ≤ 0.2 ng/ml at 12 months.
  • 29/83 patients had an undetectable PSA level (≤ 0.05 ng/ml) at 12 months
  • Of the 13 patients who required follow-up treatment because of evident biochemical recurrence, eight were retreated with HIFU, one had salvage external beam radiotherapy, and four chose active surveillance for small-volume low-risk disease.
  • Overall, there was no evidence of disease (PSA < 0.5 μg/ml or negative biopsy if nadir not achieved) after one HIFU session in 159/172 patients (92.4 percent).
  • There was no evidence of any significant difference in outcome between patients receiving hormonal ablation prior to HIFU and those who did not.
  • There was also no significant evidence of any difference in outcome based on pre-treatment PSA, Gleason score, or clinical T stage.

Now let’s look specifically at the post-treatment sexual function data.

Among the 24 men who we know to have had some degree of potency (albeit relatively low) prior to treatment:

  • At 6 months post-treatment, with or without the use of a 5-PDE inhibitor like Viagra, only 11/24 (45.8 percent) were still potent by the same criterion of “Erections hard enough to achieve penetration a few times (much less than half the time)” or better.
  • At 12 months post-treatment this had risen to 16/24 (66.7 percent).

Among the 12 men who we know to have had a slightly higher degree of potency prior to treatment:

  • At 6 months post-treatment, with or without the use of a 5-PDE inhibitor like Viagra, 7/12 (58.3 percent) were potent by the same criterion of “Erections hard enough to achieve penetration sometimes (about half the time)” or better
  • At 12 months post-treatment this had  risen to 8/12 (66.7 percent).

In other words, about one third of the patients who were capable of some degree of sexual function prior to treatment had not recovered that capability at 12 months post-treatment — and we are not talking about “potency” in language that would be acceptable to the “man in the street”, who would reasonably expect to be capable of at least full penetration “almost always.”

At this point, the commentator asks the reader to recognize that he is not trying to make any negative statement about HIFU in emphasizing these points. Rather, he wishes to congratulate Dr. Emberton and his colleagues for providing one of the very first reports to ever document such information with such a high level of accuracy and honesty in assessing the outcomes of a new form of treatment for prostate cancer. If this group of researchers has achieved nothing else, they have set a new standard for what is and should be the standard of detail to be expected of reports on any future clinical series or clinical trial of a definitive treatment for localized prostate cancer.

What do the authors themselves conclude from the data reported. We have been careful here to use their own words in so far as possible:

  • “HIFU in the treatment of prostate cancer can result in acceptable short-term levels of cancer control.”
  • The “biochemical outcome in the first 2 years” is uniform “throughout all three risk categories, although we accept that with greater follow-up cancer control is likely to deteriorate in the high risk groups.”
  • “Nonetheless, our data remains [sic] immature and the determinants of outcome are not yet known.”
  • “[T]here is incomplete reporting of outcome” and “our evaluation of genito-urinary outcomes was limited.”
  • “The rates [of early post-treatment toxicity] are high and challenge the claim of the treatment being both minimally invasive and well tolerated.” However, “Now that suprapubic catheters are used combined with early removal, there may be a reduction in [infection and dysuria].”
  • “Most of the [occurrences of retained debris or stricture] were clustered to the early part of the series at the beginning of our learning curve” and “If rates similar to those reported in this paper had persisted we would not have wanted to continue with this treatment.”

The “New” Prostate Cancer InfoLink considers that there is only one area in this paper where the authors may have “pushed the boundaries” in reporting their results. They state in their conclusions, and in the abstract, that about 70 percent of men can expect to be potent at 1 year following treatment. We would consider that, based on the data actually presented in the paper, it would have been more accurate to state that (say) “about one third of men with erections capable of vaginal penetration at least some of the time prior to treatment had lost that capability at 12 months post treatment.” However, the numbers of patients on whom there was sufficient information to make meaningful judgments was small, and we clearly need better information about pre- and post-treatment ED in men who are treated with HIFU.

Once again, the “New” Prostate Cancer InfoLink would congratulate Dr. Emberton and his colleagues on the quality of the data reported in this study. We truly hope that it sets a minimal standard for others to follow in the future.

7 Responses

  1. The authors have given more information that has been lacking about this therapy and it begins to define the negative side of treatment. What is needed, however, is longer follow-up and until that exists we do not know if this is a reasonable alternative compared to other treatment options.

  2. It would be nice to see a comparison of other treatments, such as proton beam therapy, utilizing similar criteria and over time (1 year, 2 years, 5 years, etc.). It would make a nice, informative, and helpful database.

  3. My stats were T1c, PSA 7, Gleason 6, volume 3.15, so I was a good candidate for HIFU. My catheter came out yesterday, 12 days after treatment, and I am urinating easily at about 70% of normal stream. This all seems quite fantastic to me. I am even having to keep my mind off of sex to avoid an erection! Upon their recommendation I have been on Cialis as a therapy for 3 days. We will have to see about real “performance”. I am enthusiastic about this method and optimistic about long term, especially based on the informative report above. I am convinced that at least for now this is the best method and that radiation should be used only in the absence of alternative treatments.

    Thanks, Peter

  4. I am 6 months post-HIFU. PSA reduced from 3.7 to 0.8 to 0.4 so far. The main issue has been slower urine stream and more frequent urinating. I am hoping that there is no stricture or, if there is necrotic tissue, it comes out. Is there a simple scan to see why stream is weaker? Also, this site says the IPSS deteriorated thru 6 months, but then resolved itself. Hopefully, my weak stream will resolve itself as well. Thanks.

  5. Dear Mike:

    I am not aware of any “simple scan” that can be used to analyze why your urine stream is weak. Presumably a cystoscopic examination might help to expain this. At 6 months post-HIFU, however, you really do need to get some clear guidance from your urologist.

  6. I am currently investigating different procedures for prostate cancer. I have a PSA of 7.05 and a Gleason score of 3 + 4 = 7 in only one of my 12 biopsies. The other scores were 3 + 3 = 6 in 11 biopsies. I would like more current info on HIFU.

    Thanks for your help!

  7. If you enter “HIFU” into the Search function at the top of this page, you with get links to many recent articles on HIFU.

    With 12/12 biopsy cores positive for cancer, it would be my entirely personal opinion that HIFU might not be the best of choices for your treatment; I would be concerned that we have limited information of the effectiveness of HIFU on cancers that extensive within the prostate. However, you really need to go an consult with a physician who specializes in HIFU about this.

    You do understand that to have HIFU you would have to go outside the USA to be treated and that you would have to pay for this yourself, don’t you? HIFU is not approved for the treatment of prostate cancer here in the US.

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